“To sleep, perchance to dream- ay, there’s the rub.”
— Hamlet (III, i, 65-68), Shakespeare
The great diversity of surgical methods for Deep Brain Stimulation (DBS) lead implantation raises interesting issues. A neurologist looking in from the outside would have to ask the question, are all of the implantation approaches right? To be sure, even in medicine, there is a movement towards an individualization of therapies that will result in an increased diversity of medical management. Hopefully, such individualization will still be based on fundamental and unchanging principles. The question of whether or not the diversity of surgical approaches is the result of such specification of principles applied to the individual or reflects the lack of established fundamental principles.
To answer such questions, it is helpful to first settle on the fundamental questions. To be sure, the primary goal of DBS is to insert the lead into the targeted location for optimal benefit with minimal risk and discomfort. However, a global consensus on this primary goal may deflect the need to discuss the specifics involved in achieving optimal placement. Deflecting such discussions would render the stated goal a little more than a “glittering generality”. In this and subsequent issues of this newsletter, various issues regarding the achievement of accurate placement with minimal risk and maximal patient comfort and benefit will be explored.
One issue shaping the debate regarding DBS lead implantation surgery relates to whether the procedure is done with the patient awake or asleep. Remarkable advances in neuro-anesthesia have made sedation very safe. Further, many patient candidates for DBS are older with numerous co-morbidities, including cognitive or psychological problems, consequent to the underlying disease being treated. The last thing a surgical team wants to do is wrestle with an initially cooperative patient who has become a conscious, agitated, disoriented, and combative patient later in the procedure. However, with proper patient selection and pre-operative education, the situation described above is rare. This author has been involved in many conscious DBS surgeries with patients ranging in age from 10 to 82 years without difficulty. Nevertheless, sedation is always kept close at hand for those rare and unfortunate events.
It is reasonable to believe that less stress during DBS helps to improve post-operative recovery. This has certainly been this author’s experience, especially when moving from simultaneous bilateral lead implantations, which take a considerable amount of time and creates a considerable amount of stress, to unilateral staged procedures. Interestingly, recent experience suggests that for many patients, unilateral DBS may be sufficient to provide patients with an acceptable quality of life. It may in fact delay the time or even necessity of a second DBS lead implantation surgery.
Ceteris paribus, all other things being equal, asleep surgery is preferable. The question is what is given up in exchange? While access to the regional neuroanatomy may not change (in fact, with intraoperative imaging, the detection of brain shift has improved); access to the neurophysiology does. The question becomes whether the change in access to the neurophysiology affects the probability of accurate placement; meaning the placement that maximizes benefit and minimizes the probability of adverse effects that would limit therapy. (The issue of accuracy versus precision in targeting will be addressed in later newsletters.)
Too often, access to neurophysiology is narrowly considered in terms of microelectrode recordings of extracellular action potentials (MERs). However, this is just one form of access to the neurophysiology. Perhaps the most important access to the neurophysiology is test stimulation through the DBS lead(s). It is helpful to know that the patient will not experience any adverse effects from DBS before the surgical site is closed. In this author’s experience, the degree of benefit during intraoperative DBS testing often underestimates the benefit subsequently achieved in the post-operative care clinic.
Depending on the type of anesthesia utilized, considerable physiological information can be obtained through DBS testing. For example, the appearance of a dysconjugate gaze when targeting the subthalamic nucleus (STN) suggests that the electrical field is stimulating the nerve roots of the oculomotor complex, indicating that the DBS lead is too medial. Depending on the thresholds to tonic muscle contraction at the different electrode contacts, the STN DBS lead can be determined to be too ventral, anterior or posterior, thereby indicating the direction for repositioning of the DBS lead. Similar considerations are made for DBS of the ventral intermediate nucleus of the thalamus (Vim) and the globus pallidus interna (GPi). It is important to note, and contrary to the impressions of many surgeons and physiologists, the localization of tonic muscle contraction or paresthesias, for example to the upper extremity, is not helpful in interpreting the location of homuncular representations of the target. For example, axons originating from or terminating on neurons related to the hand may be stimulated, producing paresthesias localized to the hand. However, it is just as likely that stimulation activates axons passing by onto or from other neurons representing the leg, for example. In that case, the parestheisas resulting from stimulation will be referred to the leg and provide a false localization. The problem is that the intraoperative neurophysiologist cannot know which case it is. Interested readers are referred to Montgomery Jr. EB, Intraoperative Neurophysiological Monitoring for Deep Brain Stimulation: Principles, Practice and Cases, Oxford University Press, 2015.
The patient’s subjective responses to DBS test stimulation are lost with the loss of consciousness during surgery. Most importantly, it is impossible to assess for symptomatic control. The patient will not be able to report paresthesias, which would indicate that the trajectory is too posterior in the STN or Vim. Also, the patient will not be able to report distortions of vision or phosphenes, which would indicate that the position of the DBS lead in GPi is too ventral. Further, and most importantly, patients will not be able to produce speech in order to test whether speech impairments might limit post-operative therapy. These are not inconsequential considerations. While it may be possible to stop the anesthesia prior to final closure in order to test the patient’s subjective responses, voluntary behaviors, and symptomatic responses, this can be very problematic depending on the anesthesia used and the time required for recovery. It is important to note that while patients may recover verbal communication relatively fast, the effects on the brain – as measured by electroencephalography (EEG) – may go on much longer. How these effects on the brain would affect assessment of DBS lead placement is highly problematic.
To be sure, the loss of information derived from the patient’s subjective responses to electrical stimulation, as well as the assessment of the patient’s volitional behaviors, may limit MER’s while under anesthesia. Thus, interpretation of microstimulation through the electrode tip or through the macro contact on the bipolar microelectrodes is limited to the motor responses described above for DBS lead testing. However, there is considerable information available through MERs that can be used to compensate.
Depending on the type of anesthetic agent, such as dexmedetomidine, recording of extracellular action potentials is still effective; and correlation with peripheral stimulation can still behaviorally identify the various sensori-motor regions, which are the true targets for DBS. For example, consistent changes in neuronal extracellular action potentials in response to light touch of the skin, can identify the posterior region of the ventral caudal nucleus of the thalamus (Vc) – a structure to avoid stimulating. Using MERs, it is possible to identify the anterior border of the posterior Vc and place the DBS lead accordingly, thus minimizing the risk of subsequent therapy for paresthesias. Similarly, identifying at least 5 mm of sensori-motor related STN neurons helps to ensure that the trajectory is not too posterior, placing the medial lemniscus at risk for inadvertent stimulation.
Identifying the head region of the sensori-motor homunculus in Vim helps to avoid placing the DBS lead in the head region, thereby reducing the risk of speech and swallowing problems when the patient regains consciousness and undergoes DBS. In GPi, MERs can identify the most posterior extent of neuronal activities, thus identifying the anterior boarder of the posterior limb of the internal capsule, helping to assure that the DBS lead is not placed too anterior and consequently clinically ineffective. Similarly, identifying the homuncular representation in the GPi, appropriate to the patient’s condition, helps assure that the DBS lead is not placed in an area that will decrease the probability of satisfactory clinical benefit. For example, a DBS lead placed in the leg region would likely be unhelpful in the case of cervical dystonia. Also, it is important to establish a proper location for the distal edge of the distal contact of the DBS lead. This can be determined by identifying the ventral extent of neuronal activity.
It is rare for DBS lead implantation under anesthesia to be a necessity rather than a convenience. One could argue that MERs are not only possible in asleep DBS lead implantation surgery, but it is also necessary to compensate for the information that is lost because of the loss of patient cooperation during surgery. Indeed, a study of the effects of dexmedetomidine demonstrated that the STN neuronal discharge rates were slightly increased under dexmedetomidine and the number of neurons demonstrating bursting were reduced (Krishna V, Elias G, Sammartino F, Basha D, King NK, Fasano A, Munhoz R, Kalia SK, Hodaie M, Venkatraghavan L, Lozano A, Hutchison W. The effect of dexmedetomidine on the firing properties of STN neurons in Parkinson’s Disease. Eur J Neurosci. 2015 Jun 25. doi: 0.1111/ejn.13004. PubMed PMID: 26108432.). In this author’s experience, sensori-motor driving of neurons in the STN, Vim and GPi are not affected by dexmedetomidine and thus, perhaps the most critical indicator of optimal targeting is feasible.
Unfortunately, Krishna et al. recommended against a high dose of dexmedetomidine without specifying what is a high dose or establishing any dose-response correlation. The major caution appears to be due to the difficulty of identifying bursting neurons. However, in one approach, that has demonstrated robustness in identifying targets, bursting neurons were not a consideration (Montgomery EB Jr. Microelectrode targeting of the subthalamic nucleus for deep brain stimulation surgery. Mov Disord. 2012 Sep 15;27(11):1387-91. doi: 10.1002/mds.25000. Epub 2012 Apr 16. PubMed PMID: 22508394.). Consequently, the admonition by Krishna et al. against the use of dexmedetomidine is not reasonable.